SIDE EFFECTS

The most common adverse events
reported in at least 1 indication by > 10% of adult patients treated with
FAMVIR are headache and nausea.

Clinical Trials Experience in
Adult Patients

Because clinical trials are
conducted under widely varying conditions, adverse reaction rates observed in
the clinical trials of a drug cannot be directly compared with rates in the
clinical trials of another drug and may not reflect the rates observed in practice.

* Percentage of patients with
laboratory abnormalities that were increased or decreased from baseline and
were outside of specified ranges.
†n values represent the minimum number of patients assessed for each laboratory
parameter.
NRH = Normal Range High.
NRL = Normal Range Low.

Postmarketing Experience

The adverse events listed below
have been reported during postapproval use of FAMVIR. Because these events are
reported voluntarily from a population of uncertain size, it is not always
possible to reliably estimate their frequency or establish a causal
relationship to drug exposure:

DRUG INTERACTIONS

Potential for FAMVIR to Affect
Other Drugs

The steady-state
pharmacokinetics of digoxin were not altered by concomitant administration of
multiple doses of famciclovir (500 mg three times daily). No clinically
significant effect on the pharmacokinetics of zidovudine, its metabolite
zidovudine glucuronide, or emtricitabine was observed following a single oral
dose of 500 mg famciclovir coadministered with zidovudine or emtricitabine.

An in vitro study using human
liver microsomes suggests that famciclovir is not an inhibitor of CYP3A4
enzymes.

Potential for Other Drugs to
Affect Penciclovir

No clinically significant
alterations in penciclovir pharmacokinetics were observed following single-dose
administration of 500 mg famciclovir after pretreatment with multiple doses of
allopurinol, cimetidine, theophylline, zidovudine, promethazine, when given
shortly after an antacid (magnesium and aluminum hydroxide), or concomitantly
with emtricitabine. No clinically significant effect on penciclovir
pharmacokinetics was observed following multiple-dose (three times daily)
administration of famciclovir (500 mg) with multiple doses of digoxin.

Concurrent use with probenecid
or other drugs significantly eliminated by active renal tubular secretion may
result in increased plasma concentrations of penciclovir.

The conversion of 6-deoxy
penciclovir to penciclovir is catalyzed by aldehyde oxidase. Interactions with
other drugs metabolized by this enzyme and/or inhibiting this enzyme could
potentially occur. Clinical interaction studies of famciclovir with cimetidine
and promethazine, in vitro inhibitors of aldehyde oxidase, did not show
relevant effects on the formation of penciclovir. Raloxifene, a potent aldehyde
oxidase inhibitor in vitro, could decrease the formation of penciclovir. However,
a clinical drug-drug interaction study to determine the magnitude of
interaction between penciclovir and raloxifene has not been conducted.